S 015 LBL

HIGHLIGHTS OF PRESCRIBING INFORMATION FARXIGA may require monitoring and temporary discontinuation of
These highlights do not include all the information needed to use therapy in clinical situations known to predispose to ketoacidosis. (5.2)
FARXIGA safely and effectively. See full prescribing information for • Acute Kidney Injury and Impairment in Renal Function: Consider
FARXIGA. temporarily discontinuing in settings of reduced oral intake or fluid
losses. If acute kidney injury occurs, discontinue and promptly treat.
FARXIGA® (dapagliflozin) tablets, for oral use Monitor renal function during therapy. (5.3)
Initial U.S. Approval: 2014 • Urosepsis and Pyelonephritis: Evaluate for signs and symptoms of
urinary tract infections and treat promptly, if indicated. (5.4)
---------------------------RECENT MAJOR CHANGES-------------------------- • Hypoglycemia: In patients taking insulin or an insulin secretagogue with
Dosage and Administration (2) 02/2019 FARXIGA, consider a lower dose of insulin or the insulin secretagogue
Warnings and Precautions (5.3) 02/2019 to reduce the risk of hypoglycemia. (5.5)
Warnings and Precautions (5.6) 10/2018 • Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Serious,
life-threatening cases have occurred in both females and males. Assess
--------------------------- INDICATIONS AND USAGE ------------------------- patients presenting with pain or tenderness, erythema, or swelling in the
FARXIGA is a sodium-glucose cotransporter 2 (SGLT2) inhibitor indicated genital or perineal area, along with fever or malaise. If suspected,
as an adjunct to diet and exercise to improve glycemic control in adults with institute prompt treatment. (5.6)
type 2 diabetes mellitus. (1) • Genital Mycotic Infections: Monitor and treat if indicated. (5.7)
• Increased LDL-C: Monitor and treat per standard of care. (5.8)
Limitation of use: • Bladder Cancer: An imbalance in bladder cancers was observed in
• Not for treatment of type 1 diabetes mellitus or diabetic ketoacidosis. clinical trials. FARXIGA should not be used in patients with active
(1.1) bladder cancer and should be used with caution in patients with a prior
history of bladder cancer. (5.9)
---------------------- DOSAGE AND ADMINISTRATION --------------------- • Macrovascular Outcomes: There have been no clinical studies
• Assess renal function before initiating FARXIGA and periodically establishing conclusive evidence of macrovascular risk reduction with
thereafter. (2.1) FARXIGA. (5.10)
• The recommended starting dose is 5 mg once daily, taken in the
morning, with or without food. (2.2) ------------------------------ ADVERSE REACTIONS ----------------------------
• Dose can be increased to 10 mg once daily in patients tolerating • The most common adverse reactions associated with FARXIGA (5% or
FARXIGA who require additional glycemic control. (2.2) greater incidence) were female genital mycotic infections,
• Use of FARXIGA is not recommended when the eGFR is less than nasopharyngitis, and urinary tract infections. (6.1)
45 mL/min/1.73 m2. (2.3)
To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca
--------------------- DOSAGE FORMS AND STRENGTHS ------------------- at 1-800- 236-9933 or FDA at 1-800-FDA-1088 or
• Tablets: 5 mg and 10 mg (3) www.fda.gov/medwatch.
------------------------------ CONTRAINDICATIONS ---------------------------- ----------------------- USE IN SPECIFIC POPULATIONS ---------------------

• History of serious hypersensitivity reaction to FARXIGA. (4) • Pregnancy: Advise females of the potential risk to a fetus especially
during the second and third trimesters. (8.1)
• Severe renal impairment, end-stage renal disease, or dialysis. (4)
• Lactation: FARXIGA is not recommended when breastfeeding. (8.2)
----------------------- WARNINGS AND PRECAUTIONS --------------------- • Geriatrics: Higher incidence of adverse reactions related to reduced
• Hypotension: Before initiating FARXIGA, assess volume status and intravascular volume. (5.1, 8.5)
correct hypovolemia in the elderly, in patients with renal impairment or • Renal Impairment: Higher incidence of adverse reactions related to
low systolic blood pressure, and in patients on diuretics. Monitor for reduced intravascular volume and renal function. (5.3, 6.1, 8.6)
signs and symptoms during therapy. (5.1, 6.1)
• Ketoacidosis: Assess patients who present with signs and symptoms of See 17 for PATIENT COUNSELING INFORMATION and Medication
metabolic acidosis for ketoacidosis regardless of blood glucose level. If Guide.
suspected, discontinue FARXIGA, evaluate and treat promptly. Before Revised: 02/2019
initiating FARXIGA, consider risk factors for ketoacidosis. Patients on
FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE 7 DRUG INTERACTIONS
1.1 Limitation of Use 7.1 Positive Urine Glucose Test
2 DOSAGE AND ADMINISTRATION 7.2 Interference with 1,5-anhydroglucitol (1,5-AG) Assay
2.1 Prior to Initiation of FARXIGA 8 USE IN SPECIFIC POPULATIONS
2.2 Recommended Dosage 8.1 Pregnancy
2.3 Patients with Renal Impairment 8.2 Lactation
3 DOSAGE FORMS AND STRENGTHS 8.4 Pediatric Use
4 CONTRAINDICATIONS 8.5 Geriatric Use
5 WARNINGS AND PRECAUTIONS 8.6 Renal Impairment
5.1 Hypotension 8.7 Hepatic Impairment
5.2 Ketoacidosis 10 OVERDOSAGE
5.3 Acute Kidney Injury and Impairment in Renal Function 11 DESCRIPTION
5.4 Urosepsis and Pyelonephritis 12 CLINICAL PHARMACOLOGY
5.5 Hypoglycemia with Concomitant Use with Insulin and Insulin 12.1 Mechanism of Action
Secretagogues 12.2 Pharmacodynamics
5.6 Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene) 12.3 Pharmacokinetics
5.7 Genital Mycotic Infections 13 NONCLINICAL TOXICOLOGY
5.8 Increases in Low-Density Lipoprotein Cholesterol (LDL-C) 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
5.9 Bladder Cancer 14 CLINICAL STUDIES
5.10 Macrovascular Outcomes 14.1 Overview of Clinical Studies of FARXIGA for Type 2 Diabetes
6 ADVERSE REACTIONS 14.2 Monotherapy
6.1 Clinical Trials Experience 14.3 Initial Combination Therapy with Metformin XR
6.2 Postmarketing Experience 14.4 Add-On to Metformin
Reference ID: 4394882

14.5 Active Glipizide-Controlled Study Add-On to Metformin 16 HOW SUPPLIED/STORAGE AND HANDLING
14.6 Add-On Combination Therapy with Other Antidiabetic Agents 17 PATIENT COUNSELING INFORMATION
14.7 Use in Patients with Type 2 Diabetes and Moderate Renal Impairment
*Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
FARXIGA (dapagliflozin) is indicated as an adjunct to diet and exercise to improve glycemic control in
adults with type 2 diabetes mellitus [see Clinical Studies (14)].
1.1 Limitation of Use

FARXIGA is not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic
ketoacidosis.
2 DOSAGE AND ADMINISTRATION
2.1 Prior to Initiation of FARXIGA

Assess renal function prior to initiation of FARXIGA therapy and periodically thereafter [see Warnings
and Precautions (5.3)].
In patients with volume depletion, correct this condition prior to initiation of FARXIGA [see Warnings
and Precautions (5.1), Use in Specific Populations (8.5, 8.6)].
2.2 Recommended Dosage

The recommended starting dose of FARXIGA is 5 mg once daily, taken in the morning, with or without
food. In patients tolerating FARXIGA 5 mg once daily who require additional glycemic control, the dose
can be increased to 10 mg once daily.
2.3 Patients with Renal Impairment

No dose adjustment is needed in patients with an eGFR greater than or equal to 45 mL/min/1.73 m2.
Use of FARXIGA is not recommended when the eGFR is less than 45 mL/min/1.73 m2 [see Warnings
and Precautions (5.3) and Use in Specific Populations (8.6)].
FARXIGA is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m2 [see

Contraindications (4)].
3 DOSAGE FORMS AND STRENGTHS
• FARXIGA 5 mg tablets are yellow, biconvex, round, film-coated tablets with “5” engraved on one
side and “1427” engraved on the other side.
• FARXIGA 10 mg tablets are yellow, biconvex, diamond-shaped, film-coated tablets with “10”
engraved on one side and “1428” engraved on the other side.
4 CONTRAINDICATIONS
• History of a serious hypersensitivity reaction to FARXIGA [see Adverse Reactions (6.1)].

• Severe renal impairment, (eGFR less than 30 mL/min/1.73 m2) end-stage renal disease (ESRD), or
patients on dialysis [see Use in Specific Populations (8.6)].

5 WARNINGS AND PRECAUTIONS
5.1 Hypotension
FARXIGA causes intravascular volume contraction. Symptomatic hypotension can occur after initiating
FARXIGA [see Adverse Reactions (6.1)] particularly in patients with impaired renal function (eGFR less
than 60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics. Before initiating FARXIGA in
patients with one or more of these characteristics, volume status should be assessed and corrected.
Monitor for signs and symptoms of hypotension after initiating therapy.
5.2 Ketoacidosis
Reports of ketoacidosis, a serious life-threatening condition requiring urgent hospitalization have been
identified in postmarketing surveillance in patients with type 1 and type 2 diabetes mellitus receiving
sodium-glucose cotransporter 2 (SGLT2) inhibitors, including FARXIGA. Fatal cases of ketoacidosis
have been reported in patients taking FARXIGA. FARXIGA is not indicated for the treatment of patients
with type 1 diabetes mellitus [see Indications and Usage (1.1)].
Patients treated with FARXIGA who present with signs and symptoms consistent with severe metabolic
acidosis should be assessed for ketoacidosis regardless of presenting blood glucose levels as ketoacidosis
associated with FARXIGA may be present even if blood glucose levels are less than 250 mg/dL. If
ketoacidosis is suspected, FARXIGA should be discontinued, the patient should be evaluated and prompt
treatment should be instituted. Treatment of ketoacidosis may require insulin, fluid and carbohydrate
replacement.
In many of the postmarketing reports, and particularly in patients with type 1 diabetes, the presence of
ketoacidosis was not immediately recognized and the institution of treatment was delayed because the
presenting blood glucose levels were below those typically expected for diabetic ketoacidosis (often less
than 250 mg/dL). Signs and symptoms at presentation were consistent with dehydration and severe
metabolic acidosis and included nausea, vomiting, abdominal pain, generalized malaise, and shortness of
breath. In some but not all cases, factors predisposing to ketoacidosis such as insulin dose reduction, acute
febrile illness, reduced caloric intake due to illness or surgery, pancreatic disorders suggesting insulin
deficiency (e.g., type 1 diabetes, history of pancreatitis or pancreatic surgery), and alcohol abuse were
identified.
Before initiating FARXIGA, consider factors in the patient history that may predispose to ketoacidosis
including pancreatic insulin deficiency from any cause, caloric restriction and alcohol abuse. In patients
treated with FARXIGA consider monitoring for ketoacidosis and temporarily discontinuing FARXIGA in
clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or
surgery).
5.3 Acute Kidney Injury and Impairment in Renal Function

FARXIGA causes intravascular volume contraction [see Warning and Precautions (5.1)], and can cause
renal impairment [see Adverse Reactions (6.1)]. There have been postmarketing reports of acute kidney
injury, some requiring hospitalization and dialysis, in patients receiving FARXIGA; some reports
involved patients younger than 65 years of age.

Before initiating FARXIGA, consider factors that may predispose patients to acute kidney injury
including hypovolemia, chronic renal insufficiency, congestive heart failure, and concomitant
medications (diuretics, ACE inhibitors, ARBs, NSAIDs). Consider temporarily discontinuing FARXIGA
in any setting of reduced oral intake (such as acute illness or fasting) or fluid losses (gastrointestinal
illness or excessive heat exposure); monitor patients for signs and symptoms of acute kidney injury. If
acute kidney injury occurs, discontinue FARXIGA promptly and institute treatment.
FARXIGA increases serum creatinine and decreases eGFR. Elderly patients and patients with impaired
renal function may be more susceptible to these changes. Adverse reactions related to renal function can
occur after initiating FARXIGA [see Adverse Reactions (6.1)]. Renal function should be evaluated prior
to initiation of FARXIGA and monitored periodically thereafter. Use of FARXIGA is not recommended
when the eGFR is less than 45 mL/min/1.73 m2 and is contraindicated in patients with an eGFR less
than 30 mL/min/1.73 m2 [see Dosage and Administration (2.3), Contraindications (4) and Use in Specific
Populations (8.6)].
5.4 Urosepsis and Pyelonephritis

There have been postmarketing reports of serious urinary tract infections including urosepsis and
pyelonephritis requiring hospitalization in patients receiving SGLT2 inhibitors, including FARXIGA.
Treatment with SGLT2 inhibitors increases the risk for urinary tract infections. Evaluate patients for signs
and symptoms of urinary tract infections and treat promptly, if indicated [see Adverse Reactions (6)].
5.5 Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues
Insulin and insulin secretagogues are known to cause hypoglycemia. FARXIGA can increase the risk of
hypoglycemia when combined with insulin or an insulin secretagogue [see Adverse Reactions (6.1)].
Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of
hypoglycemia when these agents are used in combination with FARXIGA.
5.6 Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene)

Reports of necrotizing fasciitis of the perineum (Fournier’s Gangrene), a rare but serious and life-
threatening necrotizing infection requiring urgent surgical intervention, have been identified in
postmarketing surveillance in patients with diabetes mellitus receiving SGLT2 inhibitors, including
FARXIGA. Cases have been reported in both females and males. Serious outcomes have included
hospitalization, multiple surgeries, and death.
Patients treated with FARXIGA presenting with pain or tenderness, erythema, or swelling in the genital
or perineal area, along with fever or malaise, should be assessed for necrotizing fasciitis. If suspected,
start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement.
Discontinue FARXIGA, closely monitor blood glucose levels, and provide appropriate alternative therapy
for glycemic control.
5.7 Genital Mycotic Infections

FARXIGA increases the risk of genital mycotic infections. Patients with a history of genital mycotic
infections were more likely to develop genital mycotic infections [see Adverse Reactions (6.1)]. Monitor
and treat appropriately.

5.8 Increases in Low-Density Lipoprotein Cholesterol (LDL-C)
Increases in LDL-C occur with FARXIGA [see Adverse Reactions (6.1)]. Monitor LDL-C and treat per
standard of care after initiating FARXIGA.
5.9 Bladder Cancer

Across 22 clinical studies, newly diagnosed cases of bladder cancer were reported in 10/6045 patients
(0.17%) treated with FARXIGA and 1/3512 patient (0.03%) treated with placebo/comparator. After
excluding patients in whom exposure to study drug was less than one year at the time of diagnosis of
bladder cancer, there were 4 cases with FARXIGA and no cases with placebo/comparator. Bladder cancer
risk factors and hematuria (a potential indicator of pre-existing tumors) were balanced between treatment
arms at baseline. There were too few cases to determine whether the emergence of these events is related
to FARXIGA.
There are insufficient data to determine whether FARXIGA has an effect on pre-existing bladder tumors.
Consequently, FARXIGA should not be used in patients with active bladder cancer. In patients with prior
history of bladder cancer, the benefits of glycemic control versus unknown risks for cancer recurrence
with FARXIGA should be considered.
5.10 Macrovascular Outcomes

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with
FARXIGA.
6 ADVERSE REACTIONS
The following important adverse reactions are described below and elsewhere in the labeling:
• Hypotension [see Warnings and Precautions (5.1)]

• Ketoacidosis [see Warnings and Precautions (5.2)]
• Acute Kidney Injury and Impairment in Renal Function [see Warnings and Precautions (5.3)]
• Urosepsis and Pyelonephritis [see Warnings and Precautions (5.4)]
• Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues [see Warnings and
Precautions (5.5)]
• Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene) [see Warnings and Precautions (5.6)]
• Genital Mycotic Infections [see Warnings and Precautions (5.7)]
• Increases in Low-Density Lipoprotein Cholesterol (LDL-C) [see Warnings and Precautions (5.8)]
• Bladder Cancer [see Warnings and Precautions (5.9)]
6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in
the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and
may not reflect the rates observed in clinical practice.

Pool of 12 Placebo-Controlled Studies for FARXIGA 5 and 10 mg
The data in Table 1 is derived from 12 placebo-controlled studies ranging from 12 to 24 weeks. In 4
studies FARXIGA was used as monotherapy, and in 8 studies FARXIGA was used as add-on to
background antidiabetic therapy or as combination therapy with metformin [see Clinical Studies (14)].
These data reflect exposure of 2338 patients to FARXIGA with a mean exposure duration of 21 weeks.
Patients received placebo (N=1393), FARXIGA 5 mg (N=1145), or FARXIGA 10 mg (N=1193) once
daily. The mean age of the population was 55 years and 2% were older than 75 years of age. Fifty percent
(50%) of the population were male; 81% were White, 14% were Asian, and 3% were Black or African
American. At baseline, the population had diabetes for an average of 6 years, had a mean hemoglobin
A1c (HbA1c) of 8.3%, and 21% had established microvascular complications of diabetes. Baseline renal
function was normal or mildly impaired in 92% of patients and moderately impaired in 8% of patients
(mean eGFR 86 mL/min/1.73 m2).
Table 1 shows common adverse reactions associated with the use of FARXIGA. These adverse reactions
were not present at baseline, occurred more commonly on FARXIGA than on placebo, and occurred in at
least 2% of patients treated with either FARXIGA 5 mg or FARXIGA 10 mg.
Table 1: Adverse Reactions in Placebo-Controlled Studies Reported in ≥2% of Patients Treated

with FARXIGA
Adverse Reaction % of Patients
Pool of 12 Placebo-Controlled Studies
Placebo FARXIGA 5 mg FARXIGA 10 mg

N=1393 N=1145 N=1193
Female genital mycotic infections* 1.5 8.4 6.9
Nasopharyngitis 6.2 6.6 6.3
Urinary tract infections† 3.7 5.7 4.3
Back pain 3.2 3.1 4.2
Increased urination‡ 1.7 2.9 3.8
Male genital mycotic infections§ 0.3 2.8 2.7
Nausea 2.4 2.8 2.5
Influenza 2.3 2.7 2.3
Dyslipidemia 1.5 2.1 2.5
Constipation 1.5 2.2 1.9
Discomfort with urination 0.7 1.6 2.1

Adverse Reaction % of Patients

N=1393 N=1145 N=1193
Pain in extremity 1.4 2.0 1.7
* Genital mycotic infections include the following adverse reactions, listed in order of frequency reported for
females: vulvovaginal mycotic infection, vaginal infection, vulvovaginal candidiasis, vulvovaginitis, genital
infection, genital candidiasis, fungal genital infection, vulvitis, genitourinary tract infection, vulval abscess, and
vaginitis bacterial. (N for females: Placebo=677, FARXIGA 5 mg=581, FARXIGA 10 mg=598).
† Urinary tract infections include the following adverse reactions, listed in order of frequency reported: urinary
tract infection, cystitis, Escherichia urinary tract infection, genitourinary tract infection, pyelonephritis,
trigonitis, urethritis, kidney infection, and prostatitis.
‡ Increased urination includes the following adverse reactions, listed in order of frequency reported: pollakiuria,
polyuria, and urine output increased.
§ Genital mycotic infections include the following adverse reactions, listed in order of frequency reported for
males: balanitis, fungal genital infection, balanitis candida, genital candidiasis, genital infection male, penile
infection, balanoposthitis, balanoposthitis infective, genital infection, posthitis. (N for males: Placebo=716,
FARXIGA 5 mg=564, FARXIGA 10 mg=595).
Pool of 13 Placebo-Controlled Studies for FARXIGA 10 mg

FARXIGA 10 mg was also evaluated in a larger placebo-controlled study pool. This pool combined 13
placebo-controlled studies, including 3 monotherapy studies, 9 add-on to background antidiabetic therapy
studies, and an initial combination with metformin study. Across these 13 studies, 2360 patients were
treated once daily with FARXIGA 10 mg for a mean duration of exposure of 22 weeks. The mean age of
the population was 59 years and 4% were older than 75 years. Fifty-eight percent (58%) of the population
were male; 84% were White, 9% were Asian, and 3% were Black or African American. At baseline, the
population had diabetes for an average of 9 years, had a mean HbA1c of 8.2%, and 30% had established
microvascular disease. Baseline renal function was normal or mildly impaired in 88% of patients and
moderately impaired in 11% of patients (mean eGFR 82 mL/min/1.73 m2).
Volume Depletion
FARXIGA causes an osmotic diuresis, which may lead to reductions in intravascular volume. Adverse
reactions related to volume depletion (including reports of dehydration, hypovolemia, orthostatic
hypotension, or hypotension) are shown in Table 2 for the 12-study and 13-study, short-term, placebo-
controlled pools [see Warnings and Precautions (5.1)].
Table 2: Adverse Reactions of Volume Depletion* in Clinical Studies with FARXIGA
Pool of 12 Placebo-Controlled
Pool of 13 Placebo-
Studies Controlled
Studies
Placebo FARXIGA FARXIGA Placebo FARXIGA
5 mg 10 mg 10 mg

Pool of 12 Placebo-Controlled
Pool of 13 Placebo-
Studies Controlled
Studies
Placebo FARXIGA FARXIGA Placebo FARXIGA
5 mg 10 mg 10 mg
Overall population N (%) N=1393 N=1145 N=1193 N=2295 N=2360
5 7 (0.6%) 9 (0.8%) 17 27 (1.1%)
(0.4%) (0.7%)
Patient Subgroup n (%)
Patients on loop diuretics n=55 n=40 n=31 n=267 n=236
1 0 3 (9.7%) 4 6 (2.5%)
(1.8%) (1.5%)
Patients with moderate renal impairment n=107 n=107 n=89 n=268 n=265
with eGFR ≥30 and <60 mL/min/1.73 2 1 (0.9%) 1 (1.1%) 4 5 (1.9%)
m2 (1.9%) (1.5%)
Patients ≥65 years of age n=276 n=216 n=204 n=711 n=665
1 1 (0.5%) 3 (1.5%) 6 11 (1.7%)
(0.4%) (0.8%)
*
Volume depletion includes reports of dehydration, hypovolemia, orthostatic hypotension, or hypotension.
Impairment of Renal Function

Use of FARXIGA was associated with increases in serum creatinine and decreases in eGFR (see Table 3).
In patients with normal or mildly impaired renal function at baseline, serum creatinine and eGFR returned
to baseline values at Week 24. Renal-related adverse reactions, including renal failure and blood
creatinine increase, were more frequent in patients treated with FARXIGA (see Table 4). Elderly patients
and patients with impaired renal function were more susceptible to these adverse reactions (see Table 4).
Sustained decreases in eGFR were seen in patients with moderate renal impairment (eGFR 30 to less than
60 mL/min/1.73 m2).

Table 3: Changes in Serum Creatinine and eGFR Associated with FARXIGA in the Pool of 12
Placebo-Controlled Studies and Moderate Renal Impairment Studies

N=1393 N=1145 N=1193
Baseline Mean Serum Creatinine (mg/dL) 0.853 0.860 0.847
eGFR (mL/min/1.73 m2) 86.0 85.3 86.7
Week 1 Change Serum Creatinine (mg/dL) −0.003 0.029 0.041
eGFR (mL/min/1.73 m2) 0.4 −2.9 −4.1
Week 24 Change Serum Creatinine (mg/dL) −0.005 −0.001 0.001
eGFR (mL/min/1.73 m2) 0.8 0.8 0.3
Moderate Renal Impairment Study
(eGFR 30 to less than 60 mL/min/1.73 m2)
N=84 N=83 N=85
Baseline Mean Serum Creatinine (mg/dL) 1.46 1.53 1.52
eGFR (mL/min/1.73 m2) 45.6 44.2 43.9
Week 1 Change Serum Creatinine (mg/dL) 0.01 0.13 0.18
eGFR (mL/min/1.73 m2) 0.5 −3.8 −5.5
eGFR (mL/min/1.73 m2) 0.03 −4.0 −7.4
eGFR (mL/min/1.73 m2) −2.6 −4.2 −7.3
Moderate Renal Impairment Study
(eGFR 45 to less than 60 mL/min/1.73 m2)
Placebo FARXIGA 10 mg
N=161 N=160
Baseline Mean Serum Creatinine (mg/dL) 1.25 1.25
eGFR (mL/min/1.73 m2) 53.6 53.3
Week 4 Change Serum Creatinine (mg/dL) -0.02 0.09
eGFR (mL/min/1.73 m2) 1.3 -3.8
eGFR (mL/min/1.73 m2) 1.5 -3.2
eGFR (mL/min/1.73 m2) 0.8 -2.0
Table 4: Proportion of Patients with at Least One Renal Impairment-Related Adverse Reaction
Pool of 6 Placebo-Controlled Pool of 9 Placebo-

Studies Controlled Studies
(up to 104 weeks)* (up to 104 weeks)†
Baseline Characteristic Placebo FARXIGA FARXIGA Placebo FARXIGA
5 mg 10 mg 10 mg
Overall population n=785 n=767 n=859 n=1956 n=2026
Patients (%) with at least one event 13 14 (1.8%) 16 (1.9%) 82 136 (6.7%)
10

Pool of 6 Placebo-Controlled Pool of 9 Placebo-
Studies Controlled Studies
(up to 104 weeks)* (up to 104 weeks)†
Baseline Characteristic Placebo FARXIGA FARXIGA Placebo FARXIGA
5 mg 10 mg 10 mg
(1.7%) (4.2%)
65 years of age and older n=190 n=655 n=620
Patients (%) with at least one event 4 n=162 n=159 52 87 (14.0%)
(2.1%) 5 (3.1%) 6 (3.8%) (7.9%)
eGFR ≥30 and <60 mL/min/1.73 m2 n=77 n=249 n=251
Patients (%) with at least one event 5 n=88 n=75 40 71 (28.3%)
(6.5%) 7 (8.0%) 9 (12.0%) (16.1%)
65 years of age and older and eGFR n=41 n=141 n=134
≥30 and <60 mL/min/1.73 m2 n=43 n=35
Patients (%) with at least one event 2 27 47 (35.1%)
(4.9%) 3 (7.0%) 4 (11.4%) (19.1%)
* Subset of patients from the pool of 12 placebo-controlled studies with long-term extensions.
† Subset of patients from the pool of 13 placebo-controlled studies with long-term extensions.
In the pool of 12 clinical studies a subgroup analysis assessed the safety of patients with eGFR between
30 to less than 60 mL/min/1.73 m2. At Week 24, the safety was similar to that seen in the overall
program, although a higher proportion of patients had at least one event related to renal impairment or
failure.
Fractures
In a study of patients with eGFR 30 to less than 60 mL/min/1.73 m2, 13 patients experienced bone
fractures for treatment durations up to 104 weeks. No fractures occurred in the placebo group, 5 occurred
in the FARXIGA 5 mg group, and 8 occurred in the FARXIGA 10 mg group. Eight of these 13 fractures
were in patients who had a baseline eGFR of 30 to 45 mL/min/1.73 m2. Ten of the 13 fractures were
reported within the first 52 weeks. There was no apparent pattern with respect to the anatomic site of
fracture.
Hypoglycemia
The frequency of hypoglycemia by study [see Clinical Studies (14)] is shown in Table 5. Hypoglycemia
was more frequent when FARXIGA was added to sulfonylurea or insulin [see Warnings and Precautions
(5.3)].
Table 5: Incidence of Major* and Minor† Hypoglycemia in Controlled Clinical Studies
Placebo/Active FARXIGA FARXIGA

Control 5 mg 10 mg
Monotherapy* (24 weeks) N=75 N=64 N=70
Major [n (%)] 0 0 0
Minor [n (%)] 0 0 0
Add-on to Metformin* (24 weeks) N=137 N=137 N=135
Major [n (%)] 0 0 0
Minor [n (%)] 0 2 (1.5) 1 (0.7)
11

Placebo/Active FARXIGA FARXIGA
Control 5 mg 10 mg
Active Control Add-on to Metformin versus N=408 – N=406
Glipizide (52 weeks)
Major [n (%)] 3 (0.7) – 0
Minor [n (%)] 147 (36.0) – 7 (1.7)
Add-on to Glimepiride* (24 weeks) N=146 N=145 N=151
Major [n (%)] 0 0 0
Minor [n (%)] 3 (2.1) 8 (5.5) 9 (6.0)
Add-on to Metformin and a Sulfonylurea (24 N=109 - N=109
Weeks)
Major [n (%)] 0 - 0
Minor [n (%)] 4 (3.7) - 14 (12.8)
Add-on to Pioglitazone* (24 weeks) N=139 N=141 N=140
Major [n (%)] 0 0 0
Minor [n (%)] 0 3 (2.1) 0
Add-on to DPP4 inhibitor (24 weeks) N=226 – N=225
Major [n (%)] 0 – 1 (0.4)
Minor [n (%)] 3 (1.3) – 4 (1.8)
Add-on to Insulin with or without other N=197 N=212 N=196
OADs‡ (24 weeks)
Major [n (%)] 1 (0.5) 1 (0.5) 1 (0.5)
Minor [n (%)] 67 (34.0) 92 (43.4) 79 (40.3)
* Major episodes of hypoglycemia were defined as symptomatic episodes requiring external (third party)
assistance due to severe impairment in consciousness or behavior with a capillary or plasma glucose value <54
mg/dL and prompt recovery after glucose or glucagon administration.
† Minor episodes of hypoglycemia were defined as either a symptomatic episode with a capillary or plasma
glucose measurement <63 mg/dL regardless of need for external assistance, or an asymptomatic capillary or
plasma glucose measurement <63 mg/dL that does not qualify as a major episode.
‡ OAD = oral antidiabetic therapy.
Genital Mycotic Infections

Genital mycotic infections were more frequent with FARXIGA treatment. Genital mycotic infections
were reported in 0.9% of patients on placebo, 5.7% on FARXIGA 5 mg, and 4.8% on FARXIGA 10 mg,
in the 12-study placebo-controlled pool. Discontinuation from study due to genital infection occurred in
0% of placebo-treated patients and 0.2% of patients treated with FARXIGA 10 mg. Infections were more
frequently reported in females than in males (see Table 1). The most frequently reported genital mycotic
infections were vulvovaginal mycotic infections in females and balanitis in males. Patients with a history
of genital mycotic infections were more likely to have a genital mycotic infection during the study than
those with no prior history (10.0%, 23.1%, and 25.0% versus 0.8%, 5.9%, and 5.0% on placebo,
FARXIGA 5 mg, and FARXIGA 10 mg, respectively).
Hypersensitivity Reactions
Hypersensitivity reactions (e.g., angioedema, urticaria, hypersensitivity) were reported with FARXIGA
treatment. Across the clinical program, serious anaphylactic reactions and severe cutaneous adverse
reactions and angioedema were reported in 0.2% of comparator-treated patients and 0.3% of FARXIGA
12

treated patients. If hypersensitivity reactions occur, discontinue use of FARXIGA; treat per standard of
care and monitor until signs and symptoms resolve.
Laboratory Tests
Increase in Hematocrit
In the pool of 13 placebo-controlled studies, increases from baseline in mean hematocrit values were
observed in FARXIGA-treated patients starting at Week 1 and continuing up to Week 16, when the
maximum mean difference from baseline was observed. At Week 24, the mean changes from baseline in
hematocrit were −0.33% in the placebo group and 2.30% in the FARXIGA 10 mg group. By Week 24,
hematocrit values >55% were reported in 0.4% of placebo-treated patients and 1.3% of FARXIGA
10 mg-treated patients.
Increase in Serum Inorganic Phosphorus

In the pool of 13 placebo-controlled studies, increases from baseline in mean serum phosphorus levels
were reported at Week 24 in FARXIGA-treated patients compared with placebo-treated patients (mean
increase of 0.13 versus −0.04 mg/dL, respectively). Higher proportions of patients with marked laboratory
abnormalities of hyperphosphatemia (≥5.6 mg/dL for age 17-65 years or ≥5.1 mg/dL for age ≥66 years)
were reported on FARXIGA at Week 24 (0.9% versus 1.7% for placebo and FARXIGA 10 mg,
respectively).
Increase in Low-Density Lipoprotein Cholesterol

In the pool of 13 placebo-controlled studies, changes from baseline in mean lipid values were reported in
FARXIGA-treated patients compared to placebo-treated patients. Mean percent changes from baseline at
Week 24, were 0.0% versus 2.5% for total cholesterol and −1.0% versus 2.9% for LDL cholesterol, in the
placebo and FARXIGA 10 mg groups, respectively.
Decrease in Serum Bicarbonate
In a study of concomitant therapy of FARXIGA 10 mg with exenatide extended-release (on a background

of metformin), four patients (1.7%) on concomitant therapy had a serum bicarbonate value of less than or
equal to 13 mEq/L compared to one each (0.4%) in the FARXIGA and exenatide-extended release
treatment groups [see Warnings and Precautions (5.2)].
6.2 Postmarketing Experience

Additional adverse reactions have been identified during postapproval use of FARXIGA. Because these
reactions are reported voluntarily from a population of uncertain size, it is generally not possible to
reliably estimate their frequency or establish a causal relationship to drug exposure.
• Ketoacidosis
• Acute Kidney Injury and Impairment in Renal Function
• Urosepsis and Pyelonephritis
• Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene)
• Rash
13

7 DRUG INTERACTIONS
7.1 Positive Urine Glucose Test

Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2
inhibitors as SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose
tests. Use alternative methods to monitor glycemic control.
7.2 Interference with 1,5-anhydroglucitol (1,5-AG) Assay

Monitoring glycemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are
unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Use alternative methods to
monitor glycemic control.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Based on animal data showing adverse renal effects, FARXIGA is not recommended during the second
and third trimesters of pregnancy.
Limited data with FARXIGA in pregnant women are not sufficient to determine drug-associated risk for
major birth defects or miscarriage. There are risks to the mother and fetus associated with poorly
controlled diabetes in pregnancy [see Clinical Considerations].
In animal studies, adverse renal pelvic and tubule dilatations, that were not fully reversible, were observed
in rats when dapagliflozin was administered during a period of renal development corresponding to the
late second and third trimesters of human pregnancy, at all doses tested; the lowest of which provided an
exposure 15-times the 10 mg clinical dose [see Data].
The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes
with a HbA1c greater than 7% and has been reported to be as high as 20 to 25% in women with HbA1c
greater than 10%. The estimated background risk of miscarriage for the indicated population is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in
clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical Considerations
Disease-associated maternal and/or embryo-fetal risk
Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis,
preeclampsia, spontaneous abortions, preterm delivery and delivery complications. Poorly controlled
diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.
Data
Animal Data
14

Dapagliflozin dosed directly to juvenile rats from postnatal day (PND) 21 until PND 90 at doses of 1, 15,
or 75 mg/kg/day, increased kidney weights and increased the incidence of renal pelvic and tubular
dilatations at all dose levels. Exposure at the lowest dose tested was 15 times the 10 mg clinical dose
(based on AUC). The renal pelvic and tubular dilatations observed in juvenile animals did not fully
reverse within a 1-month recovery period.
In a prenatal and postnatal development study, dapagliflozin was administered to maternal rats from
gestation day 6 through lactation day 21 at doses of 1, 15, or 75 mg/kg/day, and pups were indirectly
exposed in utero and throughout lactation. Increased incidence or severity of renal pelvic dilatation was
observed in 21-day-old pups offspring of treated dams at 75 mg/kg/day (maternal and pup dapagliflozin
exposures were 1415-times and 137-times, respectively, the human values at the 10 mg clinical dose,
based on AUC). Dose-related reductions in pup body weights were observed at greater or equal to
29-times the 10 mg clinical dose (based on AUC). No adverse effects on developmental endpoints were
noted at 1 mg/kg/day (19-times the 10 mg clinical dose, based on AUC). These outcomes occurred with
drug exposure during periods of renal development in rats that corresponds to the late second and third
trimester of human development.
In embryo-fetal development studies in rats and rabbits, dapagliflozin was administered throughout
organogenesis, corresponding to the first trimester of human pregnancy. In rats, dapagliflozin was neither
embryolethal nor teratogenic at doses up to 75 mg/kg/day (1441-times the 10 mg clinical dose, based on
AUC). Dose related effects on the rat fetus (structural abnormalities and reduced body weight) occurred
only at higher dosages, equal to or greater than 150 mg/kg (more than 2344-times the 10 mg clinical dose,
based on AUC), which were associated with maternal toxicity. No developmental toxicities were
observed in rabbits at doses up to 180 mg/kg/day (1191-times the 10 mg clinical dose, based on AUC).
8.2 Lactation
Risk Summary
There is no information regarding the presence of dapagliflozin in human milk, the effects on the
breastfed infant, or the effects on milk production. Dapagliflozin is present in the milk of lactating rats
[see Data]. However, due to species specific differences in lactation physiology, the clinical relevance of
these data are not clear. Since human kidney maturation occurs in utero and during the first 2 years of life
when lactational exposure may occur, there may be risk to the developing human kidney.
Because of the potential for serious adverse reactions in breastfed infants, advise women that use of
FARXIGA is not recommended while breastfeeding.
Data
Dapagliflozin was present in rat milk at a milk/plasma ratio of 0.49, indicating that dapagliflozin and its
metabolites are transferred into milk at a concentration that is approximately 50% of that in maternal
plasma. Juvenile rats directly exposed to dapagliflozin showed risk to the developing kidney (renal pelvic
and tubular dilatations) during maturation.
15

8.4 Pediatric Use
Safety and effectiveness of FARXIGA in pediatric patients under 18 years of age have not been
established.
8.5 Geriatric Use

No FARXIGA dosage change is recommended based on age. A total of 1424 (24%) of the 5936
FARXIGA-treated patients were 65 years and older and 207 (3.5%) patients were 75 years and older in a
pool of 21 double-blind, controlled, clinical safety and efficacy studies of FARXIGA. After controlling
for level of renal function (eGFR), efficacy was similar for patients under age 65 years and those 65 years
and older. In patients ≥65 years of age, a higher proportion of patients treated with FARXIGA had
adverse reactions related to volume depletion and renal impairment or failure compared to patients treated
with placebo [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].
8.6 Renal Impairment

In clinical studies, FARXIGA was associated with increases in serum creatinine and decreases in eGFR
[see Adverse Reactions (6.1)]. Use of FARXIGA is not recommended when eGFR is less than
45 mL/min/1.73 m2 [see Dosage and Administration (2.3), Warnings and Precautions (5.3), and Adverse
Reactions (6.1)] and is contraindicated in patients with severe renal impairment (eGFR less than
30 mL/min/1.73 m2) or ESRD [see Contraindications (4)].
FARXIGA was evaluated in two studies that included patients with moderate renal impairment (an eGFR
of 45 to less than 60 mL/min/1.73 m2[see Clinical Studies (14.7)], and an eGFR of 30 to less than
60 mL/min/1.73 m2, respectively). The safety profile of FARXIGA in the study of patients with an eGFR
of 45 to less than 60 mL/min/1.73 m2 was similar to the general population of patients with type 2
diabetes. Although patients in the FARXIGA arm had reduction in eGFR compared to the placebo arm,
eGFR generally returned towards baseline after treatment discontinuation. In the study of patients with an
eGFR 30 to less than 60 mL/min/1.73 m2, 13 patients receiving FARXIGA experienced bone fractures
and compared to none receiving placebo [see Adverse Reactions (6.1)].
8.7 Hepatic Impairment

No dose adjustment is recommended for patients with mild, moderate, or severe hepatic impairment.
However, the benefit-risk for the use of dapagliflozin in patients with severe hepatic impairment should
be individually assessed since the safety and efficacy of dapagliflozin have not been specifically studied
in this population [see Clinical Pharmacology (12.3)].
10 OVERDOSAGE
There were no reports of overdose during the clinical development program for FARXIGA.
In the event of an overdose, contact the Poison Control Center. It is also reasonable to employ supportive
measures, as dictated by the patient’s clinical status. The removal of dapagliflozin by hemodialysis has
not been studied.
16

11 DESCRIPTION
Dapagliflozin is described chemically as D-glucitol, 1,5-anhydro-1-C-[4-chloro-3-[(4

ethoxyphenyl)methyl]phenyl]-, (1S)-, compounded with (2S)-1,2-propanediol, hydrate (1:1:1). The
empirical formula is C21H25ClO6•C3H8O2•H2O and the molecular weight is 502.98. The structural formula
is:
FARXIGA is available as a film-coated tablet for oral administration containing the equivalent of 5 mg
dapagliflozin as dapagliflozin propanediol or the equivalent of 10 mg dapagliflozin as dapagliflozin
propanediol, and the following inactive ingredients: microcrystalline cellulose, anhydrous lactose,
crospovidone, silicon dioxide, and magnesium stearate. In addition, the film coating contains the
following inactive ingredients: polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and yellow
iron oxide.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action

Sodium-glucose cotransporter 2 (SGLT2), expressed in the proximal renal tubules, is responsible for the
majority of the reabsorption of filtered glucose from the tubular lumen. Dapagliflozin is an inhibitor of
SGLT2. By inhibiting SGLT2, dapagliflozin reduces reabsorption of filtered glucose and lowers the renal
threshold for glucose, and thereby increases urinary glucose excretion.
12.2 Pharmacodynamics
General
Increases in the amount of glucose excreted in the urine were observed in healthy subjects and in patients
with type 2 diabetes mellitus following the administration of dapagliflozin (see Figure 1). Dapagliflozin
doses of 5 or 10 mg per day in patients with type 2 diabetes mellitus for 12 weeks resulted in excretion of
approximately 70 grams of glucose in the urine per day at Week 12. A near maximum glucose excretion
was observed at the dapagliflozin daily dose of 20 mg. This urinary glucose excretion with dapagliflozin
also results in increases in urinary volume [see Adverse Reactions (6.1)].
17

Figure 1: Scatter Plot and Fitted Line of Change from Baseline in 24-Hour Urinary Glucose
Amount versus Dapagliflozin Dose in Healthy Subjects and Subjects with Type 2 Diabetes Mellitus
(T2DM) (Semi-Log Plot)
Cardiac Electrophysiology
Dapagliflozin was not associated with clinically meaningful prolongation of QTc interval at daily doses
up to 150 mg (15 times the recommended maximum dose) in a study of healthy subjects. In addition, no
clinically meaningful effect on QTc interval was observed following single doses of up to 500 mg
(50 times the recommended maximum dose) of dapagliflozin in healthy subjects.
12.3 Pharmacokinetics
Absorption
Following oral administration of dapagliflozin, the maximum plasma concentration (Cmax) is usually
attained within 2 hours under fasting state. The Cmax and AUC values increase dose proportionally with
increase in dapagliflozin dose in the therapeutic dose range. The absolute oral bioavailability of
dapagliflozin following the administration of a 10 mg dose is 78%. Administration of dapagliflozin with a
high-fat meal decreases its Cmax by up to 50% and prolongs Tmax by approximately 1 hour, but does not
18

alter AUC as compared with the fasted state. These changes are not considered to be clinically
meaningful and dapagliflozin can be administered with or without food.
Distribution
Dapagliflozin is approximately 91% protein bound. Protein binding is not altered in patients with renal or
hepatic impairment.
Metabolism
The metabolism of dapagliflozin is primarily mediated by UGT1A9; CYP-mediated metabolism is a
minor clearance pathway in humans. Dapagliflozin is extensively metabolized, primarily to yield
dapagliflozin 3-O-glucuronide, which is an inactive metabolite. Dapagliflozin 3-O-glucuronide accounted
for 61% of a 50 mg [14C]-dapagliflozin dose and is the predominant drug-related component in human
plasma.
Elimination
Dapagliflozin and related metabolites are primarily eliminated via the renal pathway. Following a single
50 mg dose of [14C]-dapagliflozin, 75% and 21% total radioactivity is excreted in urine and feces,
respectively. In urine, less than 2% of the dose is excreted as parent drug. In feces, approximately 15% of
the dose is excreted as parent drug. The mean plasma terminal half-life (t½) for dapagliflozin is
approximately 12.9 hours following a single oral dose of FARXIGA 10 mg.
Specific Populations
Renal Impairment
At steady state (20 mg once-daily dapagliflozin for 7 days), patients with type 2 diabetes with mild,
moderate, or severe renal impairment (as determined by eGFR) had geometric mean systemic exposures
of dapagliflozin that were 45%, 2.04-fold, and 3.03-fold higher, respectively, as compared to patients with
type 2 diabetes with normal renal function. Higher systemic exposure of dapagliflozin in patients with
type 2 diabetes mellitus with renal impairment did not result in a correspondingly higher 24-hour urinary
glucose excretion. The steady-state 24-hour urinary glucose excretion in patients with type 2 diabetes and
mild, moderate, and severe renal impairment was 42%, 80%, and 90% lower, respectively, than patients
with type 2 diabetes with normal renal function. The impact of hemodialysis on dapagliflozin exposure is
not known [see Dosage and Administration (2.2), Warnings and Precautions (5.3), Use in Specific
Populations (8.6), and Clinical Studies (14.7)].
Hepatic Impairment
In subjects with mild and moderate hepatic impairment (Child-Pugh classes A and B), mean Cmax and
AUC of dapagliflozin were up to 12% and 36% higher, respectively, as compared to healthy matched
control subjects following single-dose administration of 10 mg dapagliflozin. These differences were not
considered to be clinically meaningful. In patients with severe hepatic impairment (Child-Pugh class C),
mean Cmax and AUC of dapagliflozin were up to 40% and 67% higher, respectively, as compared to
healthy matched controls [see Use in Specific Populations (8.7)].
19

Effects of Age, Gender, Race, and Body Weight on Pharmacokinetics
Based on a population pharmacokinetic analysis, age, gender, race, and body weight do not have a
clinically meaningful effect on the pharmacokinetics of dapagliflozin and thus, no dose adjustment is
recommended.
Pediatric
Pharmacokinetics in the pediatric population has not been studied.
Drug Interactions
In Vitro Assessment of Drug Interactions

In in vitro studies, dapagliflozin and dapagliflozin 3-O-glucuronide neither inhibited CYP 1A2, 2C9,
2C19, 2D6, or 3A4, nor induced CYP 1A2, 2B6, or 3A4. Dapagliflozin is a weak substrate of the P
glycoprotein (P-gp) active transporter, and dapagliflozin 3-O-glucuronide is a substrate for the OAT3
active transporter. Dapagliflozin or dapagliflozin 3-O-glucuronide did not meaningfully inhibit P-gp,
OCT2, OAT1, or OAT3 active transporters. Overall, dapagliflozin is unlikely to affect the
pharmacokinetics of concurrently administered medications that are P-gp, OCT2, OAT1, or OAT3
substrates.
Effects of Other Drugs on Dapagliflozin

Table 6 shows the effect of coadministered drugs on the pharmacokinetics of dapagliflozin. No dose
adjustments are recommended for dapagliflozin.
Table 6: Effects of Coadministered Drugs on Dapagliflozin Systemic Exposure
Coadministered Drug Dapagliflozin Effect on Dapagliflozin

(Dose Regimen) * (Dose Exposure
Regimen)* (% Change [90% CI])
Cmax AUC†
No dosing adjustments required for the following:
Oral Antidiabetic Agents
Metformin (1000 mg) 20 mg ↔ ↔
Pioglitazone (45 mg) 50 mg ↔ ↔
Sitagliptin (100 mg) 20 mg ↔ ↔
Glimepiride (4 mg) 20 mg ↔ ↔
Voglibose (0.2 mg three times daily) 10 mg ↔ ↔
Other Medications
Hydrochlorothiazide (25 mg) 50 mg ↔ ↔
Bumetanide (1 mg) 10 mg once ↔ ↔
daily
for 7 days
Valsartan (320 mg) 20 mg ↓12% ↔
[↓3%, ↓20%]
Simvastatin (40 mg) 20 mg ↔ ↔
Anti-infective Agent
Rifampin (600 mg once daily for 6 days) 10 mg ↓7% ↓22%
20

Coadministered Drug Dapagliflozin Effect on Dapagliflozin
(Dose Regimen) * (Dose Exposure
Regimen)* (% Change [90% CI])
Cmax AUC†
[↓22%, [↓27%,
↑11%] ↓17%]
Nonsteroidal Anti-inflammatory Agent
Mefenamic Acid (loading dose of 500 mg followed by 10 mg ↑13% ↑51%
14 doses of 250 mg every 6 hours) [↑3%, ↑24%] [↑44%,
↑58%]
↔ = no change (geometric mean ratio of test: reference within 0.80 to 1.25); ↓ or ↑ = parameter was lower or
higher, respectively, with coadministration compared to dapagliflozin administered alone (geometric mean ratio of
test: reference was lower than 0.80 or higher than 1.25)
* Single dose unless otherwise noted.
† AUC = AUC(INF) for drugs given as single dose and AUC = AUC(TAU) for drugs given in multiple doses.
Effects of Dapagliflozin on Other Drugs

Table 7 shows the effect of dapagliflozin on other coadministered drugs. Dapagliflozin did not
meaningfully affect the pharmacokinetics of the coadministered drugs.
Table 7: Effects of Dapagliflozin on the Systemic Exposures of Coadministered Drugs
Coadministered Drug Dapagliflozin Effect on Coadministered Drug

(Dose Regimen)* (Dose Regimen)* Exposure
(% Change [90% CI])
Cmax AUC†
No dosing adjustments required for the following:
Oral Antidiabetic Agents
Metformin (1000 mg) 20 mg ↔ ↔
Pioglitazone (45 mg) 50 mg ↓7% ↔
[↓25%, ↑15%]
Sitagliptin (100 mg) 20 mg ↔ ↔
Glimepiride (4 mg) 20 mg ↔ ↑13%
[0%, ↑29%]
Other Medications
Hydrochlorothiazide (25 mg) 50 mg ↔ ↔
Bumetanide (1 mg) 10 mg once daily ↑13% ↑13%
for 7 days [↓2%, ↑31%] [↓1%, ↑30%]
Valsartan (320 mg) 20 mg ↓6% ↑5%
[↓24%, ↑16%] [↓15%, ↑29%]
Simvastatin (40 mg) 20 mg ↔ ↑19%
Digoxin (0.25 mg) 20 mg loading dose ↔ ↔
then 10 mg once
daily
for 7 days
Warfarin (25 mg) 20 mg loading dose ↔ ↔
then 10 mg once
daily
21

Coadministered Drug Dapagliflozin Effect on Coadministered Drug
(Dose Regimen)* (Dose Regimen)* Exposure
(% Change [90% CI])
Cmax AUC†
for 7 days
↔ = no change (geometric mean ratio of test: reference within 0.80 to 1.25); ↓ or ↑ = parameter was lower or
higher, respectively, with coadministration compared to the other medicine administered alone (geometric mean
ratio of test: reference was lower than 0.80 or higher than 1.25).
* Single dose unless otherwise noted.
† AUC = AUC(INF) for drugs given as single dose and AUC = AUC(TAU) for drugs given in multiple doses.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Dapagliflozin did not induce tumors in either mice or rats at any of the doses evaluated in 2-year
carcinogenicity studies. Oral doses in mice consisted of 5, 15, and 40 mg/kg/day in males and 2, 10 and
20 mg/kg/day in females, and oral doses in rats were 0.5, 2, and 10 mg/kg/day for both males and
females. The highest doses evaluated in mice were approximately 72 times (males) and 105 times
(females) the clinical dose of 10 mg per day based on AUC exposure. In rats, the highest dose was
approximately 131 times (males) and 186 times (females) the clinical dose of 10 mg per day, based on
AUC exposure.
Dapagliflozin was negative in the Ames mutagenicity assay and was positive in a series of in vitro
clastogenicity assays in the presence of S9 activation and at concentrations greater than or equal to
100 µg/mL. Dapagliflozin was negative for clastogenicity in a series of in vivo studies evaluating
micronuclei or DNA repair in rats at exposure multiples greater than 2100 times the clinical dose.
There was no carcinogenicity or mutagenicity signal in animal studies, suggesting that dapagliflozin does
not represent a genotoxic risk to humans.
Dapagliflozin had no effects on mating, fertility, or early embryonic development in treated male or
female rats at exposure multiples less than or equal to 1708 times and 998 times the maximum
recommended human dose in males and females, respectively.
14 CLINICAL STUDIES
14.1 Overview of Clinical Studies of FARXIGA for Type 2 Diabetes

FARXIGA has been studied as monotherapy, in combination with metformin, pioglitazone, sulfonylurea
(glimepiride), sitagliptin (with or without metformin), metformin plus a sulfonylurea, or insulin (with or
without other oral antidiabetic therapy), compared to a sulfonylurea (glipizide), and in combination with a
GLP-1 receptor agonist (exenatide extended-release) added-on to metformin. FARXIGA has also been
studied in patients with type 2 diabetes and moderate renal impairment.
Treatment with FARXIGA as monotherapy and in combination with metformin, glimepiride,

pioglitazone, sitagliptin, or insulin produced statistically significant improvements in mean change from
22

baseline at Week 24 in HbA1c compared to control. Reductions in HbA1c were seen across subgroups
including gender, age, race, duration of disease, and baseline BMI.
14.2 Monotherapy
A total of 840 treatment-naive patients with inadequately controlled type 2 diabetes participated in 2
placebo-controlled studies to evaluate the safety and efficacy of monotherapy with FARXIGA.
In 1 monotherapy study, a total of 558 treatment-naive patients with inadequately controlled diabetes
participated in a 24-week study (NCT00528372). Following a 2-week diet and exercise placebo lead-in
period, 485 patients with HbA1c ≥7% and ≤10% were randomized to FARXIGA 5 mg or FARXIGA
10 mg once daily in either the morning (QAM, main cohort) or evening (QPM), or placebo.
At Week 24, treatment with FARXIGA 10 mg QAM provided significant improvements in HbA1c and
FPG compared with placebo (see Table 8).
Table 8: Results at Week 24 (LOCF*) in a Placebo-Controlled Study of FARXIGA Monotherapy in

Patients with Type 2 Diabetes (Main Cohort AM Doses)
Efficacy Parameter FARXIGA 10 mg FARXIGA 5 mg Placebo

N=70† N=64† N=75†
HbA1c (%)
Baseline (mean) 8.0 7.8 7.8
Change from baseline (adjusted mean‡) −0.9 −0.8 −0.2
Difference from placebo (adjusted mean‡) −0.7§ −0.5
(95% CI) (−1.0, −0.4) (−0.8, −0.2)
Percent of patients achieving HbA1c <7% 50.8%¶ 44.2%¶ 31.6%
adjusted for baseline
FPG (mg/dL)
Baseline (mean) 166.6 157.2 159.9
Difference from placebo (adjusted mean‡) −24.7§ −19.9
(95% CI) (−35.7, −13.6) (−31.3, −8.5)
* LOCF: last observation (prior to rescue for rescued patients) carried forward.
† All randomized patients who took at least one dose of double-blind study medication during the short-term
double-blind period.
‡ Least squares mean adjusted for baseline value.
§ p-value <0.0001 versus placebo. Sensitivity analyses yielded smaller estimates of treatment difference with
placebo.
¶ Not evaluated for statistical significance as a result of the sequential testing procedure for the secondary
endpoints.
14.3 Initial Combination Therapy with Metformin XR

A total of 1241 treatment-naive patients with inadequately controlled type 2 diabetes (HbA1c ≥7.5% and
≤12%) participated in 2 active-controlled studies of 24-week duration to evaluate initial therapy with
FARXIGA 5 mg (NCT00643851) or 10 mg (NCT00859898) in combination with metformin extended-
release (XR) formulation.
23

In 1 study, 638 patients were randomized to 1 of 3 treatment arms following a 1-week lead-in period:
FARXIGA 10 mg plus metformin XR (up to 2000 mg per day), FARXIGA 10 mg plus placebo, or
metformin XR (up to 2000 mg per day) plus placebo. Metformin XR dose was up-titrated weekly in
500 mg increments, as tolerated, with a median dose achieved of 2000 mg.
The combination treatment of FARXIGA 10 mg plus metformin XR provided statistically significant

improvements in HbA1c and FPG compared with either of the monotherapy treatments and statistically
significant reduction in body weight compared with metformin XR alone (see Table 9 and Figure 2).
FARXIGA 10 mg as monotherapy also provided statistically significant improvements in FPG and
statistically significant reduction in body weight compared with metformin alone and was noninferior to
metformin XR monotherapy in lowering HbA1c.
Table 9: Results at Week 24 (LOCF*) in an Active-Controlled Study of FARXIGA Initial

Combination Therapy with Metformin XR
Efficacy Parameter FARXIGA FARXIGA Metformin XR

10 mg 10 mg
+ Metformin XR
N=211† N=219† N=208†
HbA1c (%)
Difference from FARXIGA (adjusted mean‡) −0.5§
(95% CI) (−0.7, −0.3)
Difference from metformin XR (adjusted −0.5§ 0.0¶
mean‡) (−0.8, −0.3) (−0.2, 0.2)
(95% CI)
Percent of patients achieving HbA1c <7% 46.6%# 31.7% 35.2%
FPG (mg/dL)
Baseline (mean) 189.6 197.5 189.9
(95% CI) (−20.9, −7.0)
Difference from metformin XR (adjusted −25.5§ −11.6#
mean‡) (−32.6, −18.5) (−18.6, −4.6)
(95% CI)
Body Weight (kg)
Difference from metformin XR (adjusted −2.0§ −1.4§
mean‡) (−2.6, −1.3) (−2.0, −0.7)
(95% CI)
§ p-value <0.0001.
24

¶ Noninferior versus metformin XR.
# p-value <0.05
Figure 2: Adjusted Mean Change from Baseline Over Time in HbA1c (%) in a 24-Week Active-
Controlled Study of FARXIGA Initial Combination Therapy with Metformin XR
In a second study, 603 patients were randomized to 1 of 3 treatment arms following a 1-week lead-in
period: FARXIGA 5 mg plus metformin XR (up to 2000 mg per day), FARXIGA 5 mg plus placebo, or
metformin XR (up to 2000 mg per day) plus placebo. Metformin XR dose was up-titrated weekly in
500 mg increments, as tolerated, with a median dose achieved of 2000 mg.
The combination treatment of FARXIGA 5 mg plus metformin XR provided statistically significant

improvements in HbA1c and FPG compared with either of the monotherapy treatments and statistically
significant reduction in body weight compared with metformin XR alone (see Table 10).
25

Table 10: Results at Week 24 (LOCF*) in an Active-Controlled Study of FARXIGA Initial
Combination Therapy with Metformin XR
Efficacy Parameter FARXIGA FARXIGA Metformin XR

5 mg 5 mg
+ Metformin XR
N=194† N=203† N=201†
HbA1c (%)
(95% CI) (−1.1, −0.6)
Difference from metformin XR (adjusted mean‡) −0.7§
(95% CI) (−0.9, −0.5)
Percent of patients achieving HbA1c <7% 52.4%¶ 22.5% 34.6%
FPG (mg/dL)
Baseline (mean) 193.4 190.8 196.7
(95% CI) (−26.7, −11.4)
(95% CI) (−35.1, −19.8)
Body Weight (kg)
(95% CI) (−2.0, −0.7)
§ p-value<0.0001.
¶ p-value <0.05.
14.4 Add-On to Metformin

A total of 546 patients with type 2 diabetes with inadequate glycemic control (HbA1c ≥7% and ≤10%)
participated in a 24-week, placebo-controlled study to evaluate FARXIGA in combination with
metformin (NCT00528879). Patients on metformin at a dose of at least 1500 mg per day were
randomized after completing a 2-week, single-blind, placebo lead-in period. Following the lead-in period,
eligible patients were randomized to FARXIGA 5 mg, FARXIGA 10 mg, or placebo in addition to their
current dose of metformin.
As add-on treatment to metformin, FARXIGA 10 mg provided statistically significant improvements in

HbA1c and FPG, and statistically significant reduction in body weight compared with placebo at Week 24
(see Table 11 and Figure 3). Statistically significant (p <0.05 for both doses) mean changes from baseline
26

in systolic blood pressure relative to placebo plus metformin were −4.5 mmHg and −5.3 mmHg with
FARXIGA 5 mg and 10 mg plus metformin, respectively.
Table 11: Results of a 24-Week (LOCF*) Placebo-Controlled Study of FARXIGA in Add-On

Combination with Metformin
Efficacy Parameter FARXIGA 10 FARXIGA 5 Placebo

mg mg +
+ Metformin + Metformin Metformin
N=135† N=137† N=137†
HbA1c (%)
Difference from placebo (adjusted mean‡) −0.5§ −0.4§
(95% CI) (−0.7, −0.3) (−0.6, −0.2)
FPG (mg/dL)
Baseline (mean) 156.0 169.2 165.6
Change from baseline at Week 24 (adjusted −23.5 −21.5 −6.0
mean‡)
(95% CI) (−25.0, −10.0) (−22.9, −8.1)
Change from baseline at Week 1 (adjusted −16.5§ −12.0§ 1.2
mean‡) (N=115) (N=121) (N=126)
Body Weight (kg)
(95% CI) (−2.6, −1.3) (−2.8, −1.5)
§ p-value <0.0001 versus placebo + metformin.
¶ p-value <0.05 versus placebo + metformin.
27

Figure 3: Adjusted Mean Change from Baseline Over Time in HbA1c (%) in a 24-Week Placebo-
Controlled Study of FARXIGA in Combination with Metformin
14.5 Active Glipizide-Controlled Study Add-On to Metformin

A total of 816 patients with type 2 diabetes with inadequate glycemic control (HbA1c >6.5% and ≤10%)
were randomized in a 52-week, glipizide-controlled, noninferiority study to evaluate FARXIGA as add-
on therapy to metformin (NCT00660907). Patients on metformin at a dose of at least 1500 mg per day
were randomized following a 2-week placebo lead-in period to glipizide or dapagliflozin (5 mg or 2.5 mg,
respectively) and were up-titrated over 18 weeks to optimal glycemic effect (FPG <110 mg/dL,
<6.1 mmol/L) or to the highest dose level (up to glipizide 20 mg and FARXIGA 10 mg) as tolerated by
patients. Thereafter, doses were kept constant, except for down-titration to prevent hypoglycemia.
At the end of the titration period, 87% of patients treated with FARXIGA had been titrated to the
maximum study dose (10 mg) versus 73% treated with glipizide (20 mg). FARXIGA led to a similar
mean reduction in HbA1c from baseline at Week 52 (LOCF), compared with glipizide, thus
demonstrating noninferiority (see Table 12). FARXIGA treatment led to a statistically significant mean
28

reduction in body weight from baseline at Week 52 (LOCF) compared with a mean increase in body
weight in the glipizide group. Statistically significant (p<0.0001) mean change from baseline in systolic
blood pressure relative to glipizide plus metformin was −5.0 mmHg with FARXIGA plus metformin.
Table 12: Results at Week 52 (LOCF*) in an Active-Controlled Study Comparing FARXIGA to

Glipizide as Add-On to Metformin
Efficacy Parameter FARXIGA Glipizide

+ Metformin + Metformin
N=400† N=401†
HbA1c (%)
Baseline (mean) 7.7 7.7
Change from baseline (adjusted mean‡) −0.5 −0.5
Difference from glipizide + metformin (adjusted mean‡) 0.0§
(95% CI) (−0.1, 0.1)
Body Weight (kg)
Change from baseline (adjusted mean‡) −3.2 1.4
Difference from glipizide + metformin (adjusted mean‡) −4.7¶
(95% CI) (−5.1, −4.2)
* LOCF: last observation carried forward.
† Randomized and treated patients with baseline and at least 1 postbaseline efficacy measurement.
§ Noninferior to glipizide + metformin.
¶ p-value <0.0001.
14.6 Add-On Combination Therapy with Other Antidiabetic Agents
Add-On Combination Therapy with a Sulfonylurea

A total of 597 patients with type 2 diabetes and inadequate glycemic control (HbA1c ≥7% and ≤10%)
were randomized in this 24-week, placebo-controlled study to evaluate FARXIGA in combination with
glimepiride (a sulfonylurea) (NCT00680745).
Patients on at least half the maximum recommended dose of glimepiride as monotherapy (4 mg) for at
least 8 weeks lead-in were randomized to FARXIGA 5 mg, FARXIGA 10 mg, or placebo in addition to
glimepiride 4 mg per day. Down-titration of glimepiride to 2 mg or 0 mg was allowed for hypoglycemia
during the treatment period; no up-titration of glimepiride was allowed.
In combination with glimepiride, FARXIGA 10 mg provided statistically significant improvement in

HbA1c, FPG, and 2-hour PPG, and statistically significant reduction in body weight compared with
placebo plus glimepiride at Week 24 (see Table 13). Statistically significant (p<0.05 for both doses) mean
changes from baseline in systolic blood pressure relative to placebo plus glimepiride were −2.8 mmHg
and −3.8 mmHg with FARXIGA 5 mg and 10 mg plus glimepiride, respectively.
Add-on Combination Therapy with Metformin and a Sulfonylurea

A total of 218 patients with type 2 diabetes and inadequate glycemic control (HbA1c ≥7% and ≤10.5%)
29

metformin and a sulfonylurea (NCT01392677). Patients on a stable dose of metformin (immediate- or
extended-release formulations) ≥1500 mg/day plus maximum tolerated dose, which must be at least half
the maximum dose, of a sulfonylurea for at least 8 weeks prior to enrollment were randomized after an 8
week placebo lead-in period to FARXIGA 10 mg or placebo. Dose-titration of FARXIGA or metformin
was not permitted during the 24–week treatment period. Down-titration of the sulfonylurea was permitted
to prevent hypoglycemia, but no up-titration was permitted. As add-on treatment to combined metformin
and a sulfonylurea, treatment with FARXIGA 10 mg provided statistically significant improvements in
HbA1c and FPG and statistically significant reduction in body weight compared with placebo at Week 24
(Table 13). A statistically significant (p <0.05) mean change from baseline in systolic blood pressure
relative to placebo in combination with metformin and a sulfonyl urea was -3.8 mmHg with FARXIGA
10 mg in combination with metformin and a sulfonylurea at Week 8.
Add-On Combination Therapy with a Thiazolidinedione

A total of 420 patients with type 2 diabetes with inadequate glycemic control (HbA1c ≥7% and ≤10.5%)
pioglitazone (a thiazolidinedione [TZD]) alone (NCT00683878). Patients on a stable dose of pioglitazone
of 45 mg per day (or 30 mg per day, if 45 mg per day was not tolerated) for 12 weeks were randomized
after a 2-week lead-in period to 5 or 10 mg of FARXIGA or placebo in addition to their current dose of
pioglitazone. Dose titration of FARXIGA or pioglitazone was not permitted during the study.
In combination with pioglitazone, treatment with FARXIGA 10 mg provided statistically significant

improvements in HbA1c, 2-hour PPG, FPG, the proportion of patients achieving HbA1c <7%, and a
statistically significant reduction in body weight compared with the placebo plus pioglitazone treatment
groups (see Table 13) at Week 24. A statistically significant (p <0.05) mean change from baseline in
systolic blood pressure relative to placebo in combination with pioglitazone was −4.5 mmHg with
FARXIGA 10 mg in combination with pioglitazone.
Add-On Combination Therapy with a DPP4 Inhibitor

A total of 452 patients with type 2 diabetes who were drug naive, or who were treated at entry with
metformin or a DPP4 inhibitor alone or in combination, and had inadequate glycemic control (HbA1c
≥7.0% and ≤10.0% at randomization), participated in a 24-week, placebo-controlled study to evaluate
FARXIGA in combination with sitagliptin (a DPP4 inhibitor) with or without metformin
(NCT00984867).
Eligible patients were stratified based on the presence or absence of background metformin (≥1500 mg
per day), and within each stratum were randomized to either FARXIGA 10 mg plus sitagliptin 100 mg
once daily, or placebo plus sitagliptin 100 mg once daily. Endpoints were tested for FARXIGA 10 mg
versus placebo for the total study group (sitagliptin with and without metformin) and for each stratum
(sitagliptin alone or sitagliptin with metformin). Thirty-seven percent (37%) of patients were drug naive,
32% were on metformin alone, 13% were on a DPP4 inhibitor alone, and 18% were on a DPP4 inhibitor
plus metformin. Dose titration of FARXIGA, sitagliptin, or metformin was not permitted during the
study.
In combination with sitagliptin (with or without metformin), FARXIGA 10 mg provided statistically

significant improvements in HbA1c, FPG, and a statistically significant reduction in body weight
30

compared with the placebo plus sitagliptin (with or without metformin) group at Week 24 (see Table 13).
These improvements were also seen in the stratum of patients who received FARXIGA 10 mg plus
sitagliptin alone (placebo-corrected mean change for HbA1c −0.56%; n=110) compared with placebo plus
sitagliptin alone (n=111), and the stratum of patients who received FARXIGA 10 mg plus sitagliptin and
metformin (placebo-corrected mean change for HbA1c −0.40; n=113) compared with placebo plus
sitagliptin with metformin (n=113).
Add-On Combination Therapy with Insulin

A total of 808 patients with type 2 diabetes who had inadequate glycemic control (HbA1c ≥7.5% and
≤10.5%) were randomized in a 24-week, placebo-controlled study to evaluate FARXIGA as add-on
therapy to insulin (NCT00673231). Patients on a stable insulin regimen, with a mean dose of at least
30 IU of injectable insulin per day, for a period of at least 8 weeks prior to enrollment and on a maximum
of 2 oral antidiabetic medications (OADs), including metformin, were randomized after completing a
2-week enrollment period to receive either FARXIGA 5 mg, FARXIGA 10 mg, or placebo in addition to
their current dose of insulin and other OADs, if applicable. Patients were stratified according to the
presence or absence of background OADs. Up- or down-titration of insulin was only permitted during the
treatment phase in patients who failed to meet specific glycemic goals. Dose modifications of blinded
study medication or OAD(s) were not allowed during the treatment phase, with the exception of
decreasing OAD(s) where there were concerns over hypoglycemia after cessation of insulin therapy.
In this study, 50% of patients were on insulin monotherapy at baseline, while 50% were on 1 or 2 OADs
in addition to insulin. At Week 24, FARXIGA 10 mg dose provided statistically significant improvement
in HbA1c and reduction in mean insulin dose, and a statistically significant reduction in body weight
compared with placebo in combination with insulin, with or without up to 2 OADs (see Table 13); the
effect of FARXIGA on HbA1c was similar in patients treated with insulin alone and patients treated with
insulin plus OAD. Statistically significant (p<0.05) mean change from baseline in systolic blood pressure
relative to placebo in combination with insulin was −3.0 mmHg with FARXIGA 10 mg in combination
with insulin.
At Week 24, FARXIGA 5 mg (−5.7 IU, difference from placebo) and 10 mg (−6.2 IU, difference from
placebo) once daily resulted in a statistically significant reduction in mean daily insulin dose (p<0.0001
for both doses) compared to placebo in combination with insulin, and a statistically significantly higher
proportion of patients on FARXIGA 10 mg (19.6%) reduced their insulin dose by at least 10% compared
to placebo (11.0%).
Table 13: Results of 24-Week (LOCF*) Placebo-Controlled Studies of FARXIGA in Combination

with Antidiabetic Agents
Efficacy Parameter FARXIGA FARXIGA Placebo

10 mg 5 mg
In Combination with Sulfonylurea (Glimepiride)
Intent-to-Treat Population N=151† N=142† N=145†
HbA1c (%)
‡
Change from baseline (adjusted mean ) −0.8 −0.6 −0.1
Difference from placebo (adjusted mean‡) −0.7¶ −0.5¶
31

10 mg 5 mg
(95% CI) (−0.9, −0.5) (−0.7, −0.3)
FPG (mg/dL)
Baseline (mean) 172.4 174.5 172.7
Difference from placebo (adjusted mean‡) (95% CI) −26.5¶ −19.3¶
(−33.5, −19.5) (−26.3, −12.2)
2-hour PPG# (mg/dL)
Baseline (mean) 329.6 322.8 324.1
Change from baseline (adjusted mean‡) −60.6 –54.5 −11.5
(−64.1, −34.1) (–58.4, −27.5)
Body Weight (kg)
(−2.2, −0.9) (−1.5, −0.2)
In Combination with Metformin and a Sulfonylurea
Intent-to-Treat Population N=108† - N=108†
HbA1c (%)
Baseline (mean) 8.08 - 8.24
Change from baseline (adjusted mean‡§) −0.86 - −0.17
Difference from placebo (adjusted mean‡§) −0.69¶ -
(95% CI) (−0.89, −0.49)
Percent of patients achieving HbA1c <7% 31.8%¶ - 11.1%
FPG (mg/dL)
Change from baseline (adjusted mean‡) −34.2 - −0.8
‡
Difference from placebo (adjusted mean ) (95% CI) −33.5 ¶
-
(−43.1, −23.8)
Body Weight (kg)
Change from baseline (adjusted mean‡) −2.65 - −0.58
‡
Difference from placebo (adjusted mean ) (95% CI) −2.07 ¶
-
(−2.79, −1.35)
In Combination with Thiazolidinedione (Pioglitazone)
Intent-to-Treat Population N=140Þ N=141Þ N=139Þ
HbA1c (%)
‡
(95% CI) (−0.8, −0.3) (−0.6, −0.2)
ß
Percent of patients achieving HbA1c <7% 38.8% 32.5%ß 22.4%
32

10 mg 5 mg
FPG (mg/dL)
Baseline (mean) 164.9 168.3 160.7
‡
(95% CI) (−32.2, −16.1) (−27.5, −11.4)
#
2-hour PPG (mg/dL)
Baseline (mean) 308.0 284.8 293.6
‡
(95% CI) (−71.1, −35.6) (−68.7, −33.2)
Body Weight (kg)
Change from baseline (adjusted mean‡) −0.1 0.1 1.6
‡
Difference from placebo (adjusted mean ) −1.8 ¶
−1.6¶
(95% CI) (−2.6, −1.0) (−2.3, −0.8)
In Combination with DPP4 Inhibitor (Sitagliptin) with or without Metformin
Intent-to-Treat Population N=223† – N=224†
HbA1c (%)
Baseline (mean) 7.90 – 7.97
Change from baseline (adjusted mean‡) −0.45 – 0.04
Difference from placebo (adjusted mean‡) −0.48¶ –
(95% CI) (−0.62, −0.34)
Patients with HbA1c decrease ≥0.7% (adjusted 35.4% – 16.6%
percent)
FPG (mg/dL)
Change from baseline at Week 24 (adjusted mean‡) −24.1 – 3.8
‡
–
(95% CI) (−34.5, −21.4)
Body Weight (kg)
Change from baseline (adjusted mean‡) −2.14 – −0.26
‡
–
(95% CI) (−2.37, −1.40)
In Combination with Insulin with or without up to 2 Oral Antidiabetic Therapies
Intent-to-Treat Population N=194† N=211† N=193†
HbA1c (%)
‡
(95% CI) (−0.7, −0.5) (−0.7, −0.4)
FPG (mg/dL)
Baseline (mean) 173.7 NTÀ 170.0
Change from baseline (adjusted mean‡) −21.7 NTÀ 3.3
‡
NTÀ
(95% CI) (−34.3, −15.8)
33

10 mg 5 mg
Body Weight (kg)
Change from baseline (adjusted mean‡) −1.7 −1.0 0.0
(95% CI) (−2.2, −1.2) (−1.5, −0.5)
† Randomized and treated patients with baseline and at least 1 post baseline efficacy measurement.
‡ Least squares mean adjusted for baseline value based on an ANCOVA model.
§ Least squares mean adjusted for baseline value based on a longitudinal repeated measures model.
¶ p-value <0.0001 versus placebo.
# 2-hour PPG level as a response to a 75-gram oral glucose tolerance test (OGTT).
Þ All randomized patients who took at least one dose of double-blind study medication during the short-term,
ß p-value <0.05 versus placebo.
À NT: Not formally tested because of failing to achieve a statistically significant difference in an endpoint that
was earlier in the testing sequence.
Combination Therapy with Exenatide-Extended Release as Add-On to Metformin
A total of 694 adult patients with type 2 diabetes and inadequate glycemic control (HbA1c ≥8.0 and
≤12.0%) on metformin, were evaluated in a 28-week double-blind, active-controlled study to compare
FARXIGA in combination with exenatide extended-release (a GLP-1 receptor agonist) to FARXIGA
alone and exenatide extended-release alone, as add-on to metformin (NCT02229396). Patients on
metformin at a dose of at least 1,500 mg per day were randomized following a 1-week placebo lead-in
period to receive either FARXIGA 10 mg once daily (QD) in combination with exenatide
extended-release 2 mg once weekly (QW), FARXIGA 10 mg QD, or exenatide extended–release 2 mg
QW.
At Week 28, FARXIGA in combination with exenatide extended-release provided statistically

significantly greater reductions in HbA1c (-1.77%) compared to FARXIGA alone (-1.32%, p=0.001) and
exenatide extended-release alone (-1.42%, p=0.012). FARXIGA in combination with exenatide extended-
release provided statistically significantly greater reductions in FPG (-57.35 mg/dL) compared to
FARXIGA alone (-44.72 mg/dL, p=0.006) and exenatide extended-release alone (-40.53, p <0.001).
14.7 Use in Patients with Type 2 Diabetes and Moderate Renal Impairment
FARXIGA was assessed in two placebo-controlled studies of patients with type 2 diabetes and moderate
renal impairment.
Patients with type 2 diabetes and an eGFR between 45 to less than 60 mL/min/1.73 m2 inadequately
controlled on current diabetes therapy participated in a 24-week, double-blind, placebo-controlled clinical
study (NCT02413398). Patients were randomized to either FARXIGA 10 mg or placebo, administered
orally once daily. At Week 24, FARXIGA provided statistically significant reductions in HbA1c
compared with placebo (Table 14).
34

Table 1: Results at Week 24 of Placebo-Controlled Study for FARXIGA in Patients with Type 2
Diabetes and Renal Impairment (eGFR 45 to less than 60 mL/min/1.73 m2)
FARXIGA 10 mg Placebo
Number of patients: N=160 N=161
HbA1c (%)
Change from baseline (adjusted mean*) -0.4† -0.1
Difference from placebo (adjusted mean*) -0.3†
(95% CI) (-0.5, - 0.1)
* Least squares mean adjusted for baseline value; at Week 24, HbA1c was missing for 5.6% and 6.8% of
individuals treated with FARXIGA and placebo, respectively. Retrieved dropouts, i.e. observed HbA1c at Week
24 from subjects who discontinued treatment, were used to impute missing values in HbA1c.
† p-value =0.008 versus placebo
16 HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
FARXIGA (dapagliflozin) tablets have markings on both sides and are available in the strengths and
packages listed in Table 15.
Table 15: FARXIGA Tablet Presentations
Tablet Film-Coated Tablet Package NDC

Strength Tablet Markings Size Code
Color/Shape
5 mg yellow, “5” engraved on one Bottles of 0310
biconvex, side and “1427” engraved on the other side 30 6205-30
round
10 mg yellow, “10” engraved on one side and “1428” Bottles of 0310
biconvex, engraved on the other side 30 6210-30
diamond-shaped
Storage and Handling

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see
USP Controlled Room Temperature].
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Hypotension
Inform patients that symptomatic hypotension may occur with FARXIGA and advise them to contact
their healthcare provider if they experience such symptoms [see Warnings and Precautions (5.1)]. Inform
patients that dehydration may increase the risk for hypotension, and to have adequate fluid intake.
35

Genital Mycotic Infections in Females (e.g., Vulvovaginitis)
Inform female patients that vaginal yeast infections may occur and provide them with information on the
signs and symptoms of vaginal yeast infections. Advise them of treatment options and when to seek
medical advice [see Warnings and Precautions (5.7)].
Ketoacidosis
Inform patients that ketoacidosis is a serious life-threatening condition. Cases of ketoacidosis have been
reported during use of FARXIGA. Instruct patients to check ketones (when possible) if symptoms
consistent with ketoacidosis occur even if blood glucose is not elevated. If symptoms of ketoacidosis
(including nausea, vomiting, abdominal pain, tiredness and labored breathing) occur, instruct patients to
discontinue FARXIGA and seek medical advice immediately [see Warnings and Precautions (5.2)].
Acute Kidney Injury
Inform patients that acute kidney injury has been reported during use of FARXIGA. Advise patients to
seek medical advice immediately if they have reduced oral intake (due to acute illness or fasting) or
increased fluid losses (due to vomiting, diarrhea, or excessive heat exposure), as it may be appropriate to
temporarily discontinue FARXIGA use in those settings [see Warnings and Precautions (5.3)].
Serious Urinary Tract Infections
Inform patients of the potential for urinary tract infections, which may be serious. Provide them with
information on the symptoms of urinary tract infections. Advise them to seek medical advice promptly if
such symptoms occur [see Warnings and Precautions (5.4)].
Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene)
Inform patients that necrotizing infections of the perineum (Fournier’s gangrene) have occurred with
FARXIGA. Counsel patients to promptly seek medical attention if they develop pain or tenderness,
redness, or swelling of the genitals or the area from the genitals back to the rectum, along with a fever
above 100.4°F or malaise [see Warnings and Precautions (5.6)].
Genital Mycotic Infections in Males (e.g., Balanitis)
Inform male patients that yeast infections of the penis (e.g., balanitis or balanoposthitis) may occur,
especially in patients with prior history. Provide them with information on the signs and symptoms of
balanitis and balanoposthitis (rash or redness of the glans or foreskin of the penis). Advise them of
treatment options and when to seek medical advice [see Warnings and Precautions (5.7)].
Hypersensitivity Reactions
Inform patients that serious hypersensitivity reactions (e.g., urticaria and angioedema) have been reported
with FARXIGA. Advise patients to immediately report any signs or symptoms suggesting allergic
reaction or angioedema, and to take no more of the drug until they have consulted prescribing physicians.
36

Bladder Cancer
Inform patients to promptly report any signs of macroscopic hematuria or other symptoms potentially
related to bladder cancer.
Pregnancy
Advise pregnant patients of the potential risk to a fetus with treatment with FARXIGA. Instruct patients
to immediately inform their healthcare provider if pregnant or planning to become pregnant [see Use in
Specific Populations (8.1)].
Lactation
Advise patients that use of FARXIGA is not recommended while breastfeeding [see Use in Specific
Populations (8.2)].
Laboratory Tests
Due to its mechanism of action, patients taking FARXIGA will test positive for glucose in their urine.
Distributed by:
AstraZeneca Pharmaceuticals LP
Wilmington, DE 19850
FARXIGA is a registered trademark of the AstraZeneca group of companies.
37

MEDICATION GUIDE
FARXIGA® (FAR-SEE-GUH)
(DAPAGLIFLOZIN)
TABLETS
What is the most important information I should know about FARXIGA?
FARXIGA can cause serious side effects, including:
• Dehydration. FARXIGA can cause some people to become dehydrated (the loss of body water and salt). Dehydration
may cause you to feel dizzy, faint, lightheaded, or weak, especially when you stand up (orthostatic hypotension). You
may be at a higher risk of dehydration if you:
o have low blood pressure
o take medicines to lower your blood pressure, including water pills (diuretics)
o are 65 years of age or older
o are on a low salt diet
o have kidney problems
• Vaginal yeast infection. Women who take FARXIGA may get vaginal yeast infections. Symptoms of a vaginal yeast
infection include:
o vaginal odor
o white or yellowish vaginal discharge (discharge may be lumpy or look like cottage cheese)
o vaginal itching
• Yeast infection of the penis (balanitis). Men who take FARXIGA may get a yeast infection of the skin around the
penis. Certain men who are not circumcised may have swelling of the penis that makes it difficult to pull back the skin
around the tip of the penis. Other symptoms of yeast infection of the penis include:
o redness, itching, or swelling of the penis
o rash of the penis
o foul smelling discharge from the penis
o pain in the skin around the penis
Talk to your healthcare provider about what to do if you get symptoms of a yeast infection of the vagina or penis. Your
healthcare provider may suggest you use an over-the-counter antifungal medicine. Talk to your healthcare provider right
away if you use an over-the-counter antifungal medication and your symptoms do not go away.
• Bladder cancer. In studies of FARXIGA in people with diabetes, bladder cancer occurred in a few more people who
were taking FARXIGA than in people who were taking other diabetes medications. There were too few cases to know
if bladder cancer was related to FARXIGA. You should not take FARXIGA if you have bladder cancer. Tell your
healthcare provider right away if you have any of the following symptoms:
o blood or a red color in your urine o pain while you urinate
What is FARXIGA?
FARXIGA is a prescription medicine used along with diet and exercise to lower blood sugar in adults with type 2 diabetes.
FARXIGA is not for people with type 1 diabetes.
FARXIGA is not for people with diabetic ketoacidosis (increased ketones in your blood or urine).
It is not known if FARXIGA is safe and effective in children younger than 18 years of age.
Who should not take FARXIGA?
Do not take FARXIGA if you:
• are allergic to dapagliflozin or any of the ingredients in FARXIGA. See the end of this Medication Guide for a list of
ingredients in FARXIGA. Symptoms of a serious allergic reaction to FARXIGA may include skin rash, raised red
patches on your skin (hives), swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or
swallowing.
If you have any of these symptoms, stop taking FARXIGA and contact your healthcare provider or go to the nearest
hospital emergency room right away.
• have severe kidney problems or are on dialysis.

What should I tell my healthcare provider before taking FARXIGA?
Before you take FARXIGA, tell your healthcare provider if you:
• have type 1 diabetes or have had diabetic ketoacidosis.
• have kidney problems.
• have liver problems.
• have a history of urinary tract infections or problems urinating.
• have or have had bladder cancer.
• are going to have surgery.
• are eating less due to illness, surgery or a change in your diet.
• have or have had problems with your pancreas, including pancreatitis or surgery on your pancreas.
• drink alcohol very often, or drink a lot of alcohol in the short term (“binge” drinking).
• are pregnant or plan to become pregnant. FARXIGA may harm your unborn baby. If you become pregnant while taking
FARXIGA, your healthcare provider may switch you to a different medicine to control your blood sugar. Talk to your
healthcare provider about the best way to control your blood sugar if you plan to become pregnant or while you are
pregnant.
• are breastfeeding or plan to breastfeed. It is not known if FARXIGA passes into your breast milk. You should not
breastfeed if you take FARXIGA.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines,
vitamins, and herbal supplements.
How should I take FARXIGA?
• Take FARXIGA exactly as your healthcare provider tells you to take it.
• Do not change your dose of FARXIGA without talking to your healthcare provider.
• Take FARXIGA by mouth 1 time each day, with or without food.
• When your body is under some types of stress, such as fever, trauma (such as a car accident), infection, or surgery,
the amount of diabetes medicine you need may change. Tell your healthcare provider right away if you have any of
these conditions and follow your healthcare provider’s instructions.
• Stay on your prescribed diet and exercise program while taking FARXIGA.
• Your healthcare provider may do certain blood tests before you start FARXIGA and during your treatment.
• Your healthcare provider will check your diabetes with regular blood tests, including your blood sugar levels and your
HbA1c.
• Follow your healthcare provider’s instructions for treating low blood sugar (hypoglycemia). Talk to your healthcare
provider if low blood sugar is a problem for you.
• If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and
take the medicine at the next regularly scheduled time. Do not take 2 doses of FARXIGA at the same time.
• If you take too much FARXIGA, call your healthcare provider or go to the nearest emergency room right away.
What are the possible side effects of FARXIGA? FARXIGA may cause serious side effects, including:
See “What is the most important information I should know about FARXIGA?”
• Ketoacidosis (increased ketones in your blood or urine). Ketoacidosis has happened in people who have type 1
diabetes or type 2 diabetes, during treatment with FARXIGA. Ketoacidosis is a serious condition, which may need to
be treated in a hospital. Ketoacidosis may lead to death. Ketoacidosis can happen with FARXIGA even if your
blood sugar is less than 250 mg/dL. Stop taking FARXIGA and call your healthcare provider right away if you
get any of the following symptoms:
o nausea o tiredness
o vomiting o trouble breathing
o stomach area (abdominal) pain
If you get any of these symptoms during treatment with FARXIGA, if possible check for ketones in your urine, even if
your blood sugar is less than 250 mg/dL.
• Kidney problems. Sudden kidney injury has happened to people taking FARXIGA. Talk to your doctor right away if
you:
• reduce the amount of food or liquid you drink for example, if you are sick and cannot eat or
• you start to lose liquids from your body for example, from vomiting, diarrhea or being in the sun too long.
• Serious urinary tract infections. Serious urinary tract infections that may lead to hospitalization have happened in
people who are taking FARXIGA. Tell your doctor if you have any signs or symptoms of a urinary tract infection such
as a burning feeling when passing urine, a need to urinate often, the need to urinate right away, pain in the lower part
of your stomach (pelvis), or blood in the urine. Sometimes people also may have a fever, back pain, nausea or
vomiting.
2

• Low blood sugar (hypoglycemia). If you take FARXIGA with another medicine that can cause low blood sugar, such
as a sulfonylurea or insulin, your risk of getting low blood sugar is higher. The dose of your sulfonylurea medicine or
insulin may need to be lowered while you take FARXIGA. Signs and symptoms of low blood sugar may include:
o headache o weakness o confusion
o shaking or feeling jittery o drowsiness o dizziness
o irritability o sweating o hunger
o fast heartbeat
• A rare but serious bacterial infection that causes damage to the tissue under the skin (necrotizing fasciitis) in
the area between and around the anus and genitals (perineum). Necrotizing fasciitis of the perineum has
happened in women and men who take FARXIGA. Necrotizing fasciitis of the perineum may lead to hospitalization,
may require multiple surgeries, and may lead to death. Seek medical attention immediately if you have fever or
you are feeling very week, tired or uncomfortable (malaise) and you develop any of the following symptoms in
the area between and around the anus and genitals:
o pain or tenderness o swelling o redness of skin (erythema)
• Increased fats in your blood (bad cholesterol or LDL)
The most common side effects of FARXIGA include:
• vaginal yeast infections and yeast infections of the penis
• stuffy or runny nose and sore throat
• changes in urination, including urgent need to urinate more often, in larger amounts, or at night
These are not all the possible side effects of FARXIGA. For more information, ask your healthcare provider or pharmacist.
Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA
1088.
How should I store FARXIGA?
Store FARXIGA at room temperature between 68°F to 77°F (20°C to 25°C).
General information about the safe and effective use of FARXIGA
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use FARXIGA for
a condition for which it is not prescribed. Do not give FARXIGA to other people, even if they have the same symptoms you
have. It may harm them.
This Medication Guide summarizes the most important information about FARXIGA. If you would like more information,
talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about FARXIGA that is
written for healthcare professionals.
For more information about FARXIGA, go to www.farxiga.com or call 1-800-236-9933.
What are the ingredients in FARXIGA?
Active ingredient: dapagliflozin.
Inactive ingredients: microcrystalline cellulose, anhydrous lactose, crospovidone, silicon dioxide, and magnesium
stearate. The film coating contains: polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and yellow iron oxide.
Distributed by: AstraZeneca Pharmaceuticals LP Wilmington, DE 19850
FARXIGA is a registered trademark of the AstraZeneca group of companies.
This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised 10/2018

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HIGHLIGHTS OF PRESCRIBING INFORMATION FARXIGA may require monitoring and temporary discontinuation of

------------------------------ CONTRAINDICATIONS ----------------------------­ ----------------------- USE IN SPECIFIC POPULATIONS ---------------------­

FULL PRESCRIBING INFORMATION: CONTENTS*

Reference ID: 4394882

Reference ID: 4394882

1 INDICATIONS AND USAGE

1.1 Limitation of Use

2 DOSAGE AND ADMINISTRATION

2.1 Prior to Initiation of FARXIGA

2.2 Recommended Dosage

2.3 Patients with Renal Impairment

FARXIGA is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m2 [see

3 DOSAGE FORMS AND STRENGTHS

• History of a serious hypersensitivity reaction to FARXIGA [see Adverse Reactions (6.1)].

Reference ID: 4394882

5.3 Acute Kidney Injury and Impairment in Renal Function

Reference ID: 4394882

5.4 Urosepsis and Pyelonephritis

5.6 Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene)

5.7 Genital Mycotic Infections

Reference ID: 4394882

5.9 Bladder Cancer

5.10 Macrovascular Outcomes

• Hypotension [see Warnings and Precautions (5.1)]

6.1 Clinical Trials Experience

Reference ID: 4394882

Table 1: Adverse Reactions in Placebo-Controlled Studies Reported in ≥2% of Patients Treated

Adverse Reaction % of Patients

Pool of 12 Placebo-Controlled Studies

Placebo FARXIGA 5 mg FARXIGA 10 mg

Female genital mycotic infections* 1.5 8.4 6.9

Nasopharyngitis 6.2 6.6 6.3

Urinary tract infections† 3.7 5.7 4.3

Back pain 3.2 3.1 4.2

Increased urination‡ 1.7 2.9 3.8

Male genital mycotic infections§ 0.3 2.8 2.7

Nausea 2.4 2.8 2.5

Influenza 2.3 2.7 2.3

Dyslipidemia 1.5 2.1 2.5

Constipation 1.5 2.2 1.9

Discomfort with urination 0.7 1.6 2.1

Reference ID: 4394882

Pool of 12 Placebo-Controlled Studies

Placebo FARXIGA 5 mg FARXIGA 10 mg

Pain in extremity 1.4 2.0 1.7

Pool of 13 Placebo-Controlled Studies for FARXIGA 10 mg

Table 2: Adverse Reactions of Volume Depletion* in Clinical Studies with FARXIGA

Reference ID: 4394882

Impairment of Renal Function

Reference ID: 4394882

Pool of 12 Placebo-Controlled Studies

Pool of 6 Placebo-Controlled Pool of 9 Placebo-

Reference ID: 4394882

Table 5: Incidence of Major* and Minor† Hypoglycemia in Controlled Clinical Studies

Placebo/Active FARXIGA FARXIGA

Reference ID: 4394882

Genital Mycotic Infections

Reference ID: 4394882

Increase in Serum Inorganic Phosphorus

Increase in Low-Density Lipoprotein Cholesterol

Decrease in Serum Bicarbonate

In a study of concomitant therapy of FARXIGA 10 mg with exenatide extended-release (on a background

6.2 Postmarketing Experience

------------------------------ CONTRAINDICATIONS ---------------------------- ----------------------- USE IN SPECIFIC POPULATIONS ---------------------

Dapagliflozin is described chemically as D-glucitol, 1,5-anhydro-1-C-[4-chloro-3-[(4